PMID- 37354899
OWN - NLM
STAT- MEDLINE
DCOM- 20230824
LR  - 20240213
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 58
IP  - 16
DP  - 2023 Aug 21
TI  - Loss of TJP1 disrupts gastrulation patterning and increases differentiation 
      toward the germ cell lineage in human pluripotent stem cells.
PG  - 1477-1488.e5
LID - S1534-5807(23)00265-4 [pii]
LID - 10.1016/j.devcel.2023.05.019 [doi]
AB  - Biological patterning events that occur early in development establish proper 
      tissue morphogenesis. Identifying the mechanisms that guide these patterning 
      events is necessary in order to understand the molecular drivers of development 
      and disease and to build tissues in vitro. In this study, we use an in vitro 
      model of gastrulation to study the role of tight junctions and apical/basolateral 
      polarity in modulating bone morphogenic protein-4 (BMP4) signaling and 
      gastrulation-associated patterning in colonies of human pluripotent stem cells 
      (hPSCs). Disrupting tight junctions via knockdown (KD) of the scaffolding tight 
      junction protein-1 (TJP1, also known as ZO1) allows BMP4 to robustly and 
      ubiquitously activate pSMAD1/5 signaling over time, resulting in loss of the 
      patterning phenotype and marked differentiation bias of pluripotent stem cells to 
      primordial germ cell-like cells (PGCLCs). These findings give important insights 
      into how signaling events are regulated and lead to spatial emergence of diverse 
      cell types in vitro.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Vasic, Ivana
AU  - Vasic I
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA; UC Berkeley-UC San Francisco Graduate Program in 
      Bioengineering, University of California, San Francisco, San Francisco, CA 94158, 
      USA.
FAU - Libby, Ashley R G
AU  - Libby ARG
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA; Developmental and Stem Cell Biology Ph.D. Program, 
      University of California, San Francisco, San Francisco, CA 94158, USA.
FAU - Maslan, Annie
AU  - Maslan A
AD  - UC Berkeley-UC San Francisco Graduate Program in Bioengineering, University of 
      California, San Francisco, San Francisco, CA 94158, USA; Department of 
      Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; 
      Center for Computational Biology, University of California, Berkeley, Berkeley, 
      CA 94720, USA.
FAU - Bulger, Emily A
AU  - Bulger EA
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA; Developmental and Stem Cell Biology Ph.D. Program, 
      University of California, San Francisco, San Francisco, CA 94158, USA.
FAU - Zalazar, David
AU  - Zalazar D
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA.
FAU - Krakora Compagno, Martina Z
AU  - Krakora Compagno MZ
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA.
FAU - Streets, Aaron
AU  - Streets A
AD  - UC Berkeley-UC San Francisco Graduate Program in Bioengineering, University of 
      California, San Francisco, San Francisco, CA 94158, USA; Department of 
      Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; 
      Center for Computational Biology, University of California, Berkeley, Berkeley, 
      CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
FAU - Tomoda, Kiichiro
AU  - Tomoda K
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA; Center for iPS Cell Research and Application, Kyoto 
      606-8397, Japan.
FAU - Yamanaka, Shinya
AU  - Yamanaka S
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA; Center for iPS Cell Research and Application, Kyoto 
      606-8397, Japan. Electronic address: shinya.yamanaka@gladstone.ucsf.edu.
FAU - McDevitt, Todd C
AU  - McDevitt TC
AD  - Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San 
      Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, 
      University of California, San Francisco, San Francisco, CA 94158, USA. Electronic 
      address: todd.mcdevitt@gladstone.ucsf.edu.
LA  - eng
GR  - U01 HL098179/HL/NHLBI NIH HHS/United States
GR  - R01 HL114948/HL/NHLBI NIH HHS/United States
GR  - U01 HL100406/HL/NHLBI NIH HHS/United States
GR  - R01 HL130533/HL/NHLBI NIH HHS/United States
GR  - R01 HL135358/HL/NHLBI NIH HHS/United States
GR  - C06 RR018928/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230623
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (TJP1 protein, human)
RN  - 0 (Zonula Occludens-1 Protein)
SB  - IM
CIN - Nat Rev Mol Cell Biol. 2023 Aug;24(8):521. PMID: 37400588
MH  - Humans
MH  - Cell Lineage
MH  - *Gastrulation/physiology
MH  - Cell Differentiation
MH  - *Pluripotent Stem Cells
MH  - Germ Cells
MH  - Zonula Occludens-1 Protein/genetics/metabolism
PMC - PMC10529434
MID - NIHMS1913345
OTO - NOTNLM
OT  - BMP4
OT  - PGCLCs
OT  - TJP1
OT  - cell signaling
OT  - epiblast
OT  - gastrulation
OT  - pSMAD1
OT  - tight junctions
COIS- Declaration of interests I.V. is the founder and Chief Executive Officer of Vitra 
      Labs, Inc. K.T. is on the scientific advisory board of I Peace, Inc., without 
      salary. S.Y. is a scientific advisor to iPS Academia Japan, Orizuru Therapeutics, 
      and Altos Labs without salary. T.C.M. is Vice President of Cell Engineering at 
      SanaX. I.V. and T.C.M. are inventors on a patent filing by the Gladstone 
      Institutes and the University of California, San Francisco, relating to 
      high-throughput generation of primordial germ cell-like cells (PGCLCs).
EDAT- 2023/06/25 01:08
MHDA- 2023/08/24 06:43
PMCR- 2024/08/21
CRDT- 2023/06/24 18:41
PHST- 2022/09/22 00:00 [received]
PHST- 2023/03/17 00:00 [revised]
PHST- 2023/05/26 00:00 [accepted]
PHST- 2024/08/21 00:00 [pmc-release]
PHST- 2023/08/24 06:43 [medline]
PHST- 2023/06/25 01:08 [pubmed]
PHST- 2023/06/24 18:41 [entrez]
AID - S1534-5807(23)00265-4 [pii]
AID - 10.1016/j.devcel.2023.05.019 [doi]
PST - ppublish
SO  - Dev Cell. 2023 Aug 21;58(16):1477-1488.e5. doi: 10.1016/j.devcel.2023.05.019. 
      Epub 2023 Jun 23.